AB0903 EFFICACY AND SAFETY OF NINTEDANIB IN COMBINATION WITH IMMUNOSUPPRESSIVE AGENTS FOR PROGRESSIVE FIBROSING CTD-ILD IN CLINICAL PRACTICE
Authors: Y. Ushio, R. Wakiya, T. Kameda, S. Nakashima, H. Shimada, T. Miyagi, K. Sugihara, R. Mino, M. Mizusaki, K. Chujo, H. Dobashi
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Nintedanib (NTB), a multitargeted tyrosine kinase inhibitor, has been approved in Japan for progressive fibrosing interstitial lung disease (PF-ILD) since May 2020 based on the results of the INBUILD trial [1]. This also made it a new treatment option for connective tissue disease (CTD) that are frequently complicated by ILD. On the other hand, the use of immunosuppressive agents in the treatment of ILD and primary diseases varies by disease type and country. <h3>Objectives</h3> The purpose of this study is to evaluate the efficacy and safety of NTB for progressive fibrosing CTD-ILD treated with immunosuppressive agents at a single center in Japan. <h3>Methods</h3> CTD-ILD patients who received NTB at our institution between 2020 and 2022 were extracted. Among CTD-ILD patients who received NTB, those who met the criteria for PF-ILD (1) were included in this analysis. Efficacy was evaluated by changes in forced vital capacity (FVC), and the monthly rate of decline in FVC (ΔFVC %/M) before and after the initiation of NTB. Changes in KL-6 (Krebs von den Lungen 6), a serum biomarker for ILD, were also analyzed. In addition, these efficacy parameters were compared between two groups; one group that received additional immunosuppressive agents at the same time as NTB administration (NTB+IS group), and the other group that received only NTB (NTB group). Safety was evaluated by the occurrence of adverse events within 12 months. <h3>Results</h3> There were 24 CTD-ILD patients (8 males and 16 females) who received NTB, all of whom met the criteria for PF-ILD. Patient characteristics are shown in Table 1. The most common primary disease was systemic sclerosis in 8 patients (33.3%), followed by polymyositis/dermatomyositis in 6 patients (25.0%). The mean FVC were 56.8±15.1 % and 1600.0±600.1 mL. Mean FVC increased at 6 and 12 months (ΔFVC %: +6.4 %/6M; +8.1 %/12M) and ΔFVC %/M improved from -0.65 %/M to +1.06 %/M after the initiation of NTB. Serum KL-6 decreased significantly at 6 and 12 months (ΔKL-6 U/mL: -233.7 U/mL/6M; -401.4 U/mL/12M). Eleven of the 24 patients received additional immunosuppressive agents at the same time as NTB administration (NTB+IS group). The immunosuppressive agents administrated concurrently were rituximab in 5 patients, glucocorticoids (&gt;20 mg/day prednisone or equivalent) in 4, cyclophosphamide in 2, abatacept in 2, and mycophenolate mofetil in 1. In NTB + IS group, ΔFVC %/M was significantly improved compared with the 13 patients who received only NTB (NTB group) (+1.81%/M vs. +0.20%/M, respectively) (Figure 1). Adverse events (AEs) considered to be related to treatment were diarrhea in 13 patients, nausea in 2 patients, elevations in liver enzymes in 2 patients, and headache in 1 patient, and the dose of NTB was reduced in 11 patients. No patient discontinued NTB due to AEs. <h3>Conclusion</h3> NTB for progressive fibrosing CTD-ILD appeared to be effective and safe in clinical practice. The results also suggested that the combination of NTB and immunosuppressive agents may be an effective treatment strategy. Because this was a small, single-center, observational study, further research is needed to clarify the type and timing of immunosuppressive agents to be used in combination. <h3>Reference</h3> [1]Flaherty KR, et al. N Engl J Med. 2019;381:1718-1827. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.